Speeches & Testimony

The Patient Advocate Perspective

Note: This speech was given at the 35th annual meeting of the Drug Information Association (DIA) and was printed in the Drug Information Journal, Vol. 34, 2000.

PREPARING FOR FDA ADVISORY COMMITTEE PRESENTATIONS:
VIEWS FROM FOUR PERSPECTIVES
“THE PATIENT ADVOCATE PERSPECTIVE”
ABBEY S. MEYERS, PRESIDENT
NATIONAL ORGANIZATION FOR RARE DISORDERS (NORD)
DIA ANNUAL MEETING, BALTIMORE, MD, JUNE 30, 1999

I was the consumer representative on the FDA Biological Response Modifiers Advisory Committee during the past three years, and I have just been appointed as an FDA consumer consultant for CBER, and I serve on the Xenotransplantation Subcommittee. I have the pleasure of seeing Jay Siegel quite a bit every year.

I cannot determine whether the appointment is an honor or a curse, or perhaps both. I guess I feel it is a duty akin to the young men of my generation being required to serve two years in the military. Sometimes through no fault of their own, they found themselves in the middle of a jungle, being shot at, even though they had no understanding nor interest in the politics that precipitated the war.

Conversely, I’ve appeared as a consumer to testify to other FDA advisory committees when I felt strongly about specific issues related to certain orphan drugs. In this regard, it seems to me that the advisory committee system is one of the rare demonstrations of democracy in action because it provides an opportunity for ordinary people to express their opinions directly to our government and to scientists who may sometimes forget that the scientific data, including all of their charts and graphs, are really composed of people, human beings who sacrifice a precious part of their lives when they agree to participate in clinical trials.

First let me explain that the National Organization for Rare Disorders (NORD) is a non-profit federation of approximately 140 voluntary health agencies dedicated to the identification, treatment and cure of an estimated 6,000 rare “orphan diseases.” We are the consumer organization that came together to advocate for the Orphan Drug Act, which was passed into law in 1983. Since that time, we have monitored the implementation of the law as well as the pharmaceutical industry’s participation in orphan drug development. We have also supported international efforts resulting in orphan drug legislation in Singapore, Australia, Japan and currently the European Union. Our goal is to enlist the scientific and corporate resources of all industrialized countries of the world in order to forge an international effort to alleviate the consequences of rare diseases.

The scope of the orphan disease problem is immense: In the United States there are more than 6,000 orphan diseases effecting an estimated 25 million Americans, and approximately 5,000 of these disorders are genetic. Each orphan disease affects fewer than 200,000 Americans. By the end of 1998 the FDA had designated 915 orphan drugs and 181 of them have been approved for marketing in the United States.

One of my most memorable exposures to the FDA Advisory Committee system was as a patient advocate sitting in the audience who was given less than five minutes to address the committee. I remember my thoughts at the time: Sensing that the committee members were like judges at a doctoral dissertation, testing the students. However, the students in this case were corporate experts who were absolutely certain that their data should not be questioned. The meeting evolved into a war between statisticians, and at one point I thought they would come to blows.

I remember watching people in the audience who were not consumers like me, nor scientists. Later I would understand, after listening to them talking on their cell phones in the hallway, that they were not from academia, but from Wall Street. I remember watching the FDA staff who seemed to be dueling with some of the presenters, casting doubt on every word, and other FDA staff people who seemed to be looking for compromise even though compromise did not seem possible or probable. I thought there were such vicious attacks on the scientific data that the wounds would doom the drug to oblivion. But the pendulum swung up and back throughout the day and in the end, amazingly, the committee recommended approval of the drug.

As I left the meeting, a bell boy eagerly asked me how the committee had voted. When I told him, he took a great sigh of relief. “My uncle had that disease,” he said, “and if I get it I would eat a light bulb. But maybe now I won’t have to.”

This is what patients care about. This is why I agreed to become a member of the Biological Response Modifiers Committee. But I did not really know what I was getting into. I had served on NIH Committees and Commissions, but frankly these experiences were in no way comparable to service at the FDA.

I always know when a committee meeting is drawing near. I begin to get mail from the committee staff -- lots of mail. First is the conflict of interest material that asks whether I or my institution have received any funds from certain companies. It’s not just the company that developed the drug which is the focus of the upcoming meeting, but also the companies that manufacture competing products, including generics. Then there are the affiliated companies, and subsidiary companies, as well as their competitors. There could be 50 to 100 companies listed, and your accountants have to search their ledgers to find out if your institution received any money in the past three years from any of these companies.

This is why, at the beginning of advisory committee meetings it looks like many members of the Committee have received waivers for conflict of interest. It is practically impossible to get through that list without finding out that your institution received funds from at least one of the companies in the past three years, even though you had no relationship to the funding.

Then the technical material begins to arrive. There is only one way to describe it: heavy. It is heavy reading, and it is heavy to carry, but as a bonus you must carry it all the way back to Washington for the meeting. In the past, I served on the NIH Recombinant DNA Advisory Committee (RAC). When a scientist or company submits a protocol to the RAC, they are required to provide a summary of their data in laymen’s language. But there is no similar requirement for the FDA Advisory Committees. For the most part, much of the background material might as well be written in Latin.

I truly struggle with the technical material; I try to read a bit of it every night and on the weekends. I find if try to digest it incrementally, instead of reading it all at once, I have a better chance of retaining some of the data as well as staying awake. I will not pretend to understand all of it. The BRMC reviews complicated biologicals and sometimes devices that are used in the laboratory by technicians. A layman would not ordinarily understand these products, which are on the cutting edge of science. Much of the products are related to bone marrow transplantation and cell separation, or growth factors. It is only because of my experience on the Recombinant DNA Advisory Committee that I am familiar with some of the vocabulary, but this doesn’t mean that I understand the science.

Finally, after you read the manufacturers side of the story, the FDA’s analysis arrives. It is only then that you can understand where the discrepancies arise, and why the FDA felt it necessary to ask the committee for it’s judgment.

Remember, a drug usually does not come before an Advisory Committee unless there are questions that the agency feels should be discussed by experts. A drug with clear evidence of safety and efficacy, with no questions regarding labeling, etc., will usually be approved by the agency without the involvement of an Advisory Committee. Of course companies can request an Advisory Committee meeting even though the FDA doesn’t want one; and in some cases, this may be an advantage to the company.

When the Advisory Committee meets, usually at one of the luxurious hotels in Bethesda or Rockville, I have to reveal to you that it is not fun. If you arrive well prepared, and have read all of the background material, it seems senseless for the first few hours to be spent reviewing everything you’ve already read. But that’s what happens. The company presents its side of the story, the FDA presents its side of the story, and then finally the committee is permitted to discuss the questions. FDA has prepared specific questions, but you may have others, and this is the time to ask them.

During breaks and lunch, no one but your fellow committee members are permitted to talk to you. So for the most part you feel like you have leprosy because even old friends must avoid speaking to you in the hallway. This is a very strange feeling.

What goes through my mind while I’m sitting at that table? I will confess to you that while the manufacturer and FDA are reviewing the data that I have already read, my mind sometimes wanders. I am always amazed that when we review a drug with great commercial potential, the audience is often filled to capacity, and cameras are recording every word. However, when we review important breakthrough drugs with less commercial potential, there are usually some vacant seats. When we review the status of cutting edge science, such as xenotransplantation or in utero bone marrow transplantation, which should tantalize the public’s imagination and draw reporters from all corners of the earth, the room is usually near empty. I am profoundly disappointed that reporters don’t recognize the importance of science unless the public can buy a pill or shares of stock in a company that will profit from the technology immediately.

I try to listen carefully to open discussions, especially when patients take the time to appear and testify about their experience. Sometimes they appear to be rehearsed, and you can sense that they are not talking from their heart. This is why I am always moved when a person appears because they want to tell the Committee how they were helped by a treatment, and what their improved medical condition has meant to them and their family. These witnesses are important because they can bring the discussion back to the human angle, which is often omitted from the scientific debate.

I also try to listen to FDA and the company for political clues. Is this product brought before the committee because there is a hidden agenda, or is it solely on scientific grounds? For example, sometimes there are patent questions and although information about a patent fight is not in the background materials that we receive in advance, and it may never be mentioned at the committee table, you may sometimes sense that there are these types of non-scientific factors involved. This is especially apparent when competing products are attacked by the presenting companies.

What tends to bother me, as a patient advocate, is that the in-depth scientific discussions rarely mention patients, and sometimes the welfare of patients is ignored. Too often any discussion about patients is discounted as “anecdotal.” Because most of the committee members are scientists, they tend to be more concerned about their laboratories and statistics than the humans who are supposed to be the beneficiaries of the products we are reviewing. My role on the committee is to remind them of the patients whether they want to hear about them or not.

For example, the scientists and the FDA may not see the value of approving a pill that is therapeutically equivalent to an injection. But to patients, the ability to swallow a pill is a huge advantage in comparison to a painful injection. Or they may not recognize the importance of a high dose drug when a smaller dose is currently on the market. It doesn’t occur to them, unless I remind them, that insurance companies will not pay for a patient to take a double dose of a drug that is labeled for smaller doses. Similarly, I often urge the agency to approve more liberal labeling because my primary concern is insurance reimbursement. If labeling is too narrow, insurance will not pay unless the patient’s diagnosis exactly fits the narrow criteria that FDA demands.

On the other hand, companies often ignore these questions when they design their protocols. For example, when an immunosuppressant drug is studied only on kidney transplant patients, the FDA will approve it only for renal transplants. But once it reaches the market, we all know it will be prescribed for other organ transplants. Thus people who have had a heart or liver transplant may not get reimbursed for their drug because their insurer says the unlabeled use is “experimental.”

Neither the FDA nor the drug company represent patients concerns. Let’s face it, pharmaceutical companies are not in business for their health, nor yours, nor mine. Although some of the advisory committee members are clinicians, they do not often think about what might happen once a new drug or device runs into reimbursement problems. NORD deals with these problems on a daily basis so I can pretty much predict what the problems will be. I can also object to approval of a product even though other committee members will vote for it.

In one instance, the committee voted for approval of a product that had a very high incidence of causing anaphylactic shock. I voted against it because doctors may feel secure if a warning is on the labeling, but patients never see the labeling…only doctors do. If a busy doctor forgets to tell his patient to get to a hospital immediately if symptoms appear, there are going to be a lot of dead patients. My conscience would not allow me to vote for such a dangerous product. On the other hand, I will vote in favor of a drug with severe side effects depending upon the nature of the disease, and whether informing the patient is a condition of marketing.

For example, had I been on the committee reviewing Clozaril for refractory schizophrenia, I would have voted for it because patients were required to be informed of its dangers, they were required to take a blood test every week, and at the time it was reviewed these patients had absolutely no therapeutic alternative. Similarly, NORD was probably the chief advocate for approval of Thalidomide; it is a very important drug for people who are not pregnant.

Probably the most important change that I’ve seen at FDA over the last two decades is the willingness of the agency to weigh risks against benefits. Back in the 1970’s, when I was first learning about the agency, it simply would not accept risk in the products it approved. They seemed to look at all new drugs as if they were potential Thalidomides. Today, however, the agency understands that patients who are dying are often willing to take greater risks on the chance that they might lengthen their lives or possibly avoid permanent disability. The concern is that the FDA’s pendulum does not swing too far in this direction because the risks associated with Clozaril (for example) would not be acceptable for Viagra or Rogaine. I know that FDA personnel understand the difference, but I believe they need consumers like me to remind them from time to time that FDA’s mission is both to protect and enhance the public’s health. There is a very fine line between the two.

Some Advisory Committees have consumer advocates who are experts on specific diseases. I must confess that I would at least be more knowledgeable if I were on a committee reviewing neurological drugs because I could focus on learning about the basics, like neurotransmitters. The Biological Response Modifiers Committee, however, seems to be all over the place. There is no possible way for an ordinary mortal like me to understand or even predict the area of science that will be the focus of the next meeting. I only know that when I read the background material, and when I listen to the scientific presentations, I must never forget the patients. If my allegiance is to them, and if I always focus on their welfare, I will have served them well even if the rest of the committee disagrees with me.

I believe that other consumer representatives probably feel the same way because we see our role as important even if we don’t understand some of the technical discussion. But the bottom line for all manufacturers is you cannot win the scientific arguments with influence, or filling the room with fans of your drug. You will win it with data, just good data. Show the committee that you have a safe and effective product and patient representatives will not be intimidated by those who oppose approval of your product.

Understand, however, that we will not tolerate risks associated with medicines for acne or baldness, while we may accept such risks associated with drugs for Alzheimer’s or cancer. Just be honest about the risks when you appear before the committee because if we learn about them after a drug is marketed, it erodes our trust and may make us overly cautious in the future.

When I return home after an advisory committee meeting I sometimes wonder whether I have accomplished anything. Sometimes it seems like the only “beneficiaries,” or “victims” of the committee’s decision are the Wall Street stockbrokers, not the patients. It often seems before I leave my hotel room, CNN has announced the committee’s vote. If we voted positively, the newscaster always adds verbiage quoted from the company’s press release, and the fact that FDA usually follows its committee’s recommendations. Perhaps I wouldn’t be annoyed at this scenario if I could invest in the products that I review, but I can’t.

So I have to focus on the patients -- will they benefit from the public forum discussion and from the committee’s recommendations? Sometimes the drug or device that we reviewed does not represent a major therapeutic advancement, even though reporters may describe it as the greatest medical advancement since penicillin. In these cases, the only beneficiaries will be on Wall Street. But sometimes our decisions represent life and death for certain patients because the products are unique scientific breakthroughs. Surely they would have reached the market without my two cents being injected in the committee’s deliberations. But the fact that I was there perhaps had an impact on a few words in the labeling, or the agenda for post-marketing studies may have been enhanced, or maybe I clarified an obscure factor that might eventually convince an insurance company to pay for a drug that it doesn’t want to pay for. I hope this is the value that I bring to the table at FDA Advisory Committee meetings.

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